WO2021177247A1 - Mineral absorption enhancer - Google Patents
Mineral absorption enhancer Download PDFInfo
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- WO2021177247A1 WO2021177247A1 PCT/JP2021/007771 JP2021007771W WO2021177247A1 WO 2021177247 A1 WO2021177247 A1 WO 2021177247A1 JP 2021007771 W JP2021007771 W JP 2021007771W WO 2021177247 A1 WO2021177247 A1 WO 2021177247A1
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/724—Cyclodextrins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to a mineral absorption promoter. More specifically, the present invention relates to a mineral absorption enhancer containing cyclodextrin (hereinafter, may be simply referred to as CD) as an active ingredient.
- CD mineral absorption enhancer containing cyclodextrin
- SCFAs short-chain fatty acids
- CD is an indigestible oligosaccharide, as a new alternative to this LS.
- CD is a substance having inclusion properties and is used as various components such as foods and chemicals.
- a mineral absorption promoter containing a specific cyclic tetrasaccharide and / or a sugar derivative thereof as an active ingredient in Patent Document 1, a sugar that can be contained according to a purpose such as enhancing dispersibility or increasing the amount. It is listed as one of the qualities.
- ⁇ -CD or ⁇ -CD can be contained as one of the stabilizers.
- An object of the present invention is to provide a substance having an effect of promoting mineral absorption equal to or higher than that of LS.
- CD has an effect of promoting absorption of minerals such as calcium, and have completed the present invention.
- This mineral absorption promoter could also be used as an active ingredient such as a bone mass increasing agent and a bone strength improving agent.
- the present invention relates to the mineral absorption promoters and the like shown in the following (1) to (4).
- the mineral absorption promoter of the present invention can be used as it is as a food, a health food, a quasi-drug, a pharmaceutical product, etc., or can be used as an active ingredient such as a bone mass increasing agent or a bone strength improving agent. Can be used for various purposes.
- test example It is a figure which showed the influence on the improvement of mineral absorption (test example). It is a figure which showed the influence on the bone mass increase (test example). It is a figure which showed the influence on the improvement of bone strength (test example).
- the "mineral absorption promoter" of the present invention means absorption of minerals into the body of an ingested animal by ingesting it by an animal such as a human, a mouse, a rat, a rabbit, a dog, a cat, a horse, a sheep, a monkey, or a cow.
- Such a “mineral absorption promoter” of the present invention may be any agent containing CD as an active ingredient. It may be the CD itself, or may be an agent containing other components such as a component capable of assisting mineral absorption such as LS and a component necessary for maintaining the dosage form in addition to the CD.
- the CD that can be used as the active ingredient of the "mineral absorption promoter" of the present invention may be a CD that can be safely ingested by animals, and may be a commercially available product or an independently prepared CD.
- Examples of such a CD include ⁇ -CD, ⁇ -CD, ⁇ -CD, maltosyl- ⁇ -CD, maltosyl- ⁇ -CD, maltosyl- ⁇ -CD and the like.
- One type of these CDs may be used as an active ingredient, or two or more types may be used in combination.
- Examples of commercially available ⁇ -CD include pure fiber (Kosana Co., Ltd.) and indigestible ⁇ -oligosaccharide (Kosana Co., Ltd.).
- the mineral whose absorption is promoted by the "mineral absorption promoter" of the present invention may be any mineral useful for the formation of the body of an animal, maintenance of health, etc., and for example, calcium, magnesium, iron, etc. , Copper, zinc and the like, and calcium in particular may be applicable.
- the "bone mass increasing agent” and “bone strength improving agent” of the present invention are animals ingested by animals such as humans, mice, rats, rabbits, dogs, cats, horses, sheep, monkeys, and cows. An agent that can increase the weight of bones and improve the strength of bones.
- These "bone mass increasing agent” and “bone strength improving agent” may be any agent containing the "mineral absorption promoting agent” of the present invention as an active ingredient, and the “mineral absorption promoting agent” is the CD itself. May use the CD itself as a “bone mass increasing agent” or a "bone strength improving agent”. Further, in addition to the CD itself, it may be an agent containing other components such as a component useful for increasing bone mass and bone strength, and a component necessary for maintaining a dosage form.
- the "mineral absorption promoter", "bone mass increasing agent” and “bone strength improving agent” of the present invention may be administered in an amount that is effective in the ingesting animal.
- the animal to be ingested is a human
- Example 1 Method for Producing Mineral Absorption Promoter ⁇ -CD was used as it was as a mineral absorption promoter.
- Table 1 shows the mixing ratio of the experimental feed in each group.
- the ⁇ -CD or LS content was adjusted to 5.5% in the dry feed. After stirring each powder well, 100 ml of water was added and the mixture was used as an experimental feed. Eight weeks after the start of breeding, rats in each group were fasted overnight and then dissected under isoflurane anesthesia, and the femur and cecum were removed.
- the contents of the cecum thawed at the stage of bacterial flora analysis are kneaded and homogenized, and the consignment (Technosuruga Lab Co., Ltd.) analyzes the bacterial flora using the T-RFLP method, measures the amount of SCFAs, and analyzes the pH. went.
- the total amount of SCFAs was calculated by totaling the amounts of lactic acid, succinic acid, acetic acid, propionic acid and butyric acid.
- the proportion of Lactobacillales in the ⁇ -CD group was higher than that in the NF group or LS group.
- Analysis of SCFAs levels showed that the ⁇ -CD group significantly increased lactic acid, succinic acid, acetic acid, propionic acid, n-butyric acid and total SCFAs levels compared to the NF group, and lactic acid and succinic acid compared to the LS group. It was confirmed that the amounts of acid, acetic acid, propionic acid, n-butyric acid and total SCFAs increased remarkably.
- the extracted mineral content was solubilized with 0.01 M hydrochloric acid to prepare an excretory calcium measurement sample and an ingestion calcium measurement sample.
- the calcium concentration in each sample was measured by metalloassay calcium measurement (OCPC) (Metalogenix Co., Ltd.), and calcium excretion and calcium intake were calculated by the following formulas 1 and 2. The value obtained by subtracting the blank value from these values was taken as the true calcium excretion amount or calcium intake amount.
- OCPC metalloassay calcium measurement
- the calcium absorption rate was calculated from each of these true amounts of calcium by the following formulas 3 and 4, and the results are shown in FIG.
- the group that ingested the experimental diet containing ⁇ -CD ( ⁇ -CD group) was compared with the group that ingested the experimental diet not containing ⁇ -CD or LS (NF group). It was shown that the absorption rate of calcium was significantly improved (p ⁇ 0.05). It was also confirmed that the group that ingested the experimental diet containing ⁇ -CD ( ⁇ -CD group) had a higher calcium absorption rate than the group that ingested the experimental diet containing LS (LS group). ..
- Bone strength The central part of the femoral bone whose bone mass was measured in 4 and 1) above was measured by the bone strength / skin breaking strength tester TK-252D (Muromachi Kikai Co., Ltd.) at a speed of 3 mm / min and a distance between fulcrums of 1 cm. The bone strength was examined from the measured maximum load after fracture under the conditions of. As a result, as shown in FIG. 3, it was shown that the ⁇ -CD group significantly improved the bone strength as compared with the NF group, and it was confirmed that the improvement in the bone strength was remarkable as compared with the LS group (). p ⁇ 0.05).
- CD itself has the effect of promoting the absorption of minerals such as calcium equal to or higher than that of LS. Furthermore, it was shown that CD itself has a remarkable effect on increasing bone mass and bone strength.
- the neral absorption promoter of the present invention can be used as it is as a food, a health food, a quasi-drug, a pharmaceutical product, etc., or can be used as an active ingredient such as a bone mass increasing agent or a bone strength improving agent. Can be used for various purposes.
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Abstract
Provision of a substance having an effect of enhancing mineral absorption equal to or greater than that of LS. Provided is a mineral absorption enhancer containing cyclodextrin as an active ingredient, as a substance having an effect of enhancing mineral absorption equal to or greater than that of LS. Bone mass-increasing agents, bone strength-improving agents, etc., having this mineral absorption enhancer as an active ingredient can also be provided.
Description
本発明はミネラル吸収促進剤に関する。さらに詳しくは、シクロデキストリン（以下、単にCDと示す場合がある）を有効成分として含むミネラル吸収促進剤に関する。
The present invention relates to a mineral absorption promoter. More specifically, the present invention relates to a mineral absorption enhancer containing cyclodextrin (hereinafter, may be simply referred to as CD) as an active ingredient.
ヒトの腸内細菌は腸内で食物繊維や難消化性オリゴ糖を分解し、宿主に様々な健康増進効果をもたらす短鎖脂肪酸（以下、単にSCFAｓと示す場合がある）を産生することが知られている。
難消化性オリゴ糖のひとつであるラクトスクロース（LS）はSCFAs産生量の増加に有用であることが知られており、LSを摂取することにより腸内のビフィズス菌が増加し、SCFAs産生量が増加することで、体内へのカルシウムの吸収を促進すること等が確認されている（例えば、非特許文献１参照）。 It is known that human intestinal bacteria decompose dietary fiber and indigestible oligosaccharides in the intestine to produce short-chain fatty acids (hereinafter, may be simply referred to as SCFAs) that have various health-promoting effects on the host. Has been done.
Lactosucrose (LS), which is one of the indigestible oligosaccharides, is known to be useful for increasing the production of SCFAs. Ingestion of LS increases bifidobacteria in the intestine and increases the production of SCFAs. It has been confirmed that the increase promotes the absorption of calcium into the body (see, for example, Non-Patent Document 1).
難消化性オリゴ糖のひとつであるラクトスクロース（LS）はSCFAs産生量の増加に有用であることが知られており、LSを摂取することにより腸内のビフィズス菌が増加し、SCFAs産生量が増加することで、体内へのカルシウムの吸収を促進すること等が確認されている（例えば、非特許文献１参照）。 It is known that human intestinal bacteria decompose dietary fiber and indigestible oligosaccharides in the intestine to produce short-chain fatty acids (hereinafter, may be simply referred to as SCFAs) that have various health-promoting effects on the host. Has been done.
Lactosucrose (LS), which is one of the indigestible oligosaccharides, is known to be useful for increasing the production of SCFAs. Ingestion of LS increases bifidobacteria in the intestine and increases the production of SCFAs. It has been confirmed that the increase promotes the absorption of calcium into the body (see, for example, Non-Patent Document 1).
本発明者らはこのLSに替り得る新たなものとして、難消化性オリゴ糖であるCDに着目した。
CDは包接性を有する物質であり、食品や薬品等の様々な成分として使用されている。例えば、特許文献１における“特定の環状四糖及び／又はこれらの糖質誘導体を有効成分とするミネラル吸収促進剤”に関する発明において、分散性を高めたり、増量等の目的に応じて含有できる糖質のひとつとして挙げられている。また、特許文献２における“特定のクエルセチン誘導体を有効成分として含有する骨粗鬆症治療剤”に関する発明においては、安定剤のひとつとしてα-CD又はβ-CDを含有し得ることが記載されている。 The present inventors focused on CD, which is an indigestible oligosaccharide, as a new alternative to this LS.
CD is a substance having inclusion properties and is used as various components such as foods and chemicals. For example, in the invention relating to "a mineral absorption promoter containing a specific cyclic tetrasaccharide and / or a sugar derivative thereof as an active ingredient" in Patent Document 1, a sugar that can be contained according to a purpose such as enhancing dispersibility or increasing the amount. It is listed as one of the qualities. Further, in the invention relating to "therapeutic agent for osteoporosis containing a specific quercetin derivative as an active ingredient" inPatent Document 2, it is described that α-CD or β-CD can be contained as one of the stabilizers.
CDは包接性を有する物質であり、食品や薬品等の様々な成分として使用されている。例えば、特許文献１における“特定の環状四糖及び／又はこれらの糖質誘導体を有効成分とするミネラル吸収促進剤”に関する発明において、分散性を高めたり、増量等の目的に応じて含有できる糖質のひとつとして挙げられている。また、特許文献２における“特定のクエルセチン誘導体を有効成分として含有する骨粗鬆症治療剤”に関する発明においては、安定剤のひとつとしてα-CD又はβ-CDを含有し得ることが記載されている。 The present inventors focused on CD, which is an indigestible oligosaccharide, as a new alternative to this LS.
CD is a substance having inclusion properties and is used as various components such as foods and chemicals. For example, in the invention relating to "a mineral absorption promoter containing a specific cyclic tetrasaccharide and / or a sugar derivative thereof as an active ingredient" in Patent Document 1, a sugar that can be contained according to a purpose such as enhancing dispersibility or increasing the amount. It is listed as one of the qualities. Further, in the invention relating to "therapeutic agent for osteoporosis containing a specific quercetin derivative as an active ingredient" in
しかし、これらの先行技術に示されるように、CDそのもののカルシウム等のミネラル吸収への効果については検討すらされていなかった。そこで、本発明者らはCDを用い、LSと同等又はそれ以上のミネラル吸収を促進する効果を有するものの提供を試みた。
However, as shown in these prior arts, the effect of CD itself on the absorption of minerals such as calcium has not even been examined. Therefore, the present inventors have tried to provide a CD having an effect of promoting mineral absorption equal to or higher than that of LS.
本発明はLSと同等又はそれ以上のミネラル吸収を促進する効果を有するものの提供を課題とする。
An object of the present invention is to provide a substance having an effect of promoting mineral absorption equal to or higher than that of LS.
本発明者らは、上記課題を解決するために鋭意検討を行った結果、CDがカルシウム等のミネラル吸収を促進する効果を有することを見出し、本発明を完成するに至った。このミネラル吸収促進剤は、骨量増加剤や骨強度向上剤等の有効成分として用いることも可能であった。
As a result of diligent studies to solve the above problems, the present inventors have found that CD has an effect of promoting absorption of minerals such as calcium, and have completed the present invention. This mineral absorption promoter could also be used as an active ingredient such as a bone mass increasing agent and a bone strength improving agent.
すなわち、本発明は次の（１）～（４）に示されるミネラル吸収促進剤等に関する。
（１）CDを有効成分として含むミネラル吸収促進剤。
（２）ミネラルがカルシウムである上記（１）に記載のミネラル吸収促進剤。
（３）上記（１）又は（２）に記載のミネラル吸収促進剤を有効成分として含む骨量増加剤。
（４）上記（１）又は（２）に記載のミネラル吸収促進剤を有効成分として含む骨強度向上剤。 That is, the present invention relates to the mineral absorption promoters and the like shown in the following (1) to (4).
(1) A mineral absorption promoter containing CD as an active ingredient.
(2) The mineral absorption promoter according to (1) above, wherein the mineral is calcium.
(3) A bone mass-increasing agent containing the mineral absorption-promoting agent according to (1) or (2) above as an active ingredient.
(4) A bone strength improver containing the mineral absorption promoter according to (1) or (2) above as an active ingredient.
（１）CDを有効成分として含むミネラル吸収促進剤。
（２）ミネラルがカルシウムである上記（１）に記載のミネラル吸収促進剤。
（３）上記（１）又は（２）に記載のミネラル吸収促進剤を有効成分として含む骨量増加剤。
（４）上記（１）又は（２）に記載のミネラル吸収促進剤を有効成分として含む骨強度向上剤。 That is, the present invention relates to the mineral absorption promoters and the like shown in the following (1) to (4).
(1) A mineral absorption promoter containing CD as an active ingredient.
(2) The mineral absorption promoter according to (1) above, wherein the mineral is calcium.
(3) A bone mass-increasing agent containing the mineral absorption-promoting agent according to (1) or (2) above as an active ingredient.
(4) A bone strength improver containing the mineral absorption promoter according to (1) or (2) above as an active ingredient.
本発明によりLSと同等又はそれ以上のミネラル吸収を促進する効果を有するものの提供が可能となった。本発明のミネラル吸収促進剤はそのまま食品、健康食品、医薬部外品や医薬品等として利用したり、骨量増加剤や骨強度向上剤等の有効成分として利用したりすることができ、様々な用途に使用できる。
According to the present invention, it has become possible to provide a substance having an effect of promoting mineral absorption equal to or higher than that of LS. The mineral absorption promoter of the present invention can be used as it is as a food, a health food, a quasi-drug, a pharmaceutical product, etc., or can be used as an active ingredient such as a bone mass increasing agent or a bone strength improving agent. Can be used for various purposes.
本発明の「ミネラル吸収促進剤」とは、ヒト、マウス、ラット、ウサギ、イヌ、ネコ、ウマ、ヒツジ、サル、ウシ等の動物が摂取することによって、摂取した動物の体内へのミネラルの吸収率が向上し得る剤のことをいう。このような本発明の「ミネラル吸収促進剤」はCDを有効成分として含む剤であればよい。CDそのものであってもよく、CDに加えて、さらにLS等のミネラル吸収を補助し得る成分、剤形を保つのに必要な成分等、その他の成分を含む剤であってもよい。
本発明の「ミネラル吸収促進剤」の有効成分として使用し得るCDは動物が安全に摂取できるCDであればよく、市販のものであっても、独自に調製したものであってもよい。このようなCDとしてα-CD、β-CD、γ-CD、マルトシル-α-CD、マルトシル-β-CD又はマルトシル-γ-CD等が挙げられる。これらのCDは有効成分として１種類用いてもよく、2種類以上を組み合わせて用いても良い。
市販のα-CDとして例えばピュアファイバー（株式会社コサナ）、難消化性αオリゴ糖（株式会社コサナ）等が挙げられる。 The "mineral absorption promoter" of the present invention means absorption of minerals into the body of an ingested animal by ingesting it by an animal such as a human, a mouse, a rat, a rabbit, a dog, a cat, a horse, a sheep, a monkey, or a cow. An agent that can improve the rate. Such a "mineral absorption promoter" of the present invention may be any agent containing CD as an active ingredient. It may be the CD itself, or may be an agent containing other components such as a component capable of assisting mineral absorption such as LS and a component necessary for maintaining the dosage form in addition to the CD.
The CD that can be used as the active ingredient of the "mineral absorption promoter" of the present invention may be a CD that can be safely ingested by animals, and may be a commercially available product or an independently prepared CD. Examples of such a CD include α-CD, β-CD, γ-CD, maltosyl-α-CD, maltosyl-β-CD, maltosyl-γ-CD and the like. One type of these CDs may be used as an active ingredient, or two or more types may be used in combination.
Examples of commercially available α-CD include pure fiber (Kosana Co., Ltd.) and indigestible α-oligosaccharide (Kosana Co., Ltd.).
本発明の「ミネラル吸収促進剤」の有効成分として使用し得るCDは動物が安全に摂取できるCDであればよく、市販のものであっても、独自に調製したものであってもよい。このようなCDとしてα-CD、β-CD、γ-CD、マルトシル-α-CD、マルトシル-β-CD又はマルトシル-γ-CD等が挙げられる。これらのCDは有効成分として１種類用いてもよく、2種類以上を組み合わせて用いても良い。
市販のα-CDとして例えばピュアファイバー（株式会社コサナ）、難消化性αオリゴ糖（株式会社コサナ）等が挙げられる。 The "mineral absorption promoter" of the present invention means absorption of minerals into the body of an ingested animal by ingesting it by an animal such as a human, a mouse, a rat, a rabbit, a dog, a cat, a horse, a sheep, a monkey, or a cow. An agent that can improve the rate. Such a "mineral absorption promoter" of the present invention may be any agent containing CD as an active ingredient. It may be the CD itself, or may be an agent containing other components such as a component capable of assisting mineral absorption such as LS and a component necessary for maintaining the dosage form in addition to the CD.
The CD that can be used as the active ingredient of the "mineral absorption promoter" of the present invention may be a CD that can be safely ingested by animals, and may be a commercially available product or an independently prepared CD. Examples of such a CD include α-CD, β-CD, γ-CD, maltosyl-α-CD, maltosyl-β-CD, maltosyl-γ-CD and the like. One type of these CDs may be used as an active ingredient, or two or more types may be used in combination.
Examples of commercially available α-CD include pure fiber (Kosana Co., Ltd.) and indigestible α-oligosaccharide (Kosana Co., Ltd.).
本発明の「ミネラル吸収促進剤」により吸収が促進されるミネラルには、動物の体の形成や健康維持等に有用なミネラルであればいずれものも該当し得るが、例えば、カルシウム、マグネシウム、鉄、銅、亜鉛等が挙げられ、特にカルシウムが該当し得る。
The mineral whose absorption is promoted by the "mineral absorption promoter" of the present invention may be any mineral useful for the formation of the body of an animal, maintenance of health, etc., and for example, calcium, magnesium, iron, etc. , Copper, zinc and the like, and calcium in particular may be applicable.
本発明の「骨量増加剤」や「骨強度向上剤」とは、ヒト、マウス、ラット、ウサギ、イヌ、ネコ、ウマ、ヒツジ、サル、ウシ等の動物が摂取することによって、摂取した動物の骨の重量を増加させたり、骨の強さを向上させたりし得る剤のことをいう。
これらの「骨量増加剤」や「骨強度向上剤」は、本願発明の「ミネラル吸収促進剤」を有効成分として含む剤であればよく、該「ミネラル吸収促進剤」がCDそのものである場合は、CDそのものを「骨量増加剤」や「骨強度向上剤」としてもよい。また、CDそのものに加えてさらに骨量の増加や骨強度の向上に有用な成分、剤形を保つのに必要な成分等、その他の成分を含む剤であってもよい。
本発明の「ミネラル吸収促進剤」、「骨量増加剤」や「骨強度向上剤」は摂取する動物において効果を示す量を投与すればよい。例えば、摂取する動物がヒトである場合、各剤に含まれ、摂取されるCDの量が0.001～10g/日程度となるように投与されることが好ましい。 The "bone mass increasing agent" and "bone strength improving agent" of the present invention are animals ingested by animals such as humans, mice, rats, rabbits, dogs, cats, horses, sheep, monkeys, and cows. An agent that can increase the weight of bones and improve the strength of bones.
These "bone mass increasing agent" and "bone strength improving agent" may be any agent containing the "mineral absorption promoting agent" of the present invention as an active ingredient, and the "mineral absorption promoting agent" is the CD itself. May use the CD itself as a "bone mass increasing agent" or a "bone strength improving agent". Further, in addition to the CD itself, it may be an agent containing other components such as a component useful for increasing bone mass and bone strength, and a component necessary for maintaining a dosage form.
The "mineral absorption promoter", "bone mass increasing agent" and "bone strength improving agent" of the present invention may be administered in an amount that is effective in the ingesting animal. For example, when the animal to be ingested is a human, it is preferable to administer the CD so that the amount of CD contained in each agent is about 0.001 to 10 g / day.
これらの「骨量増加剤」や「骨強度向上剤」は、本願発明の「ミネラル吸収促進剤」を有効成分として含む剤であればよく、該「ミネラル吸収促進剤」がCDそのものである場合は、CDそのものを「骨量増加剤」や「骨強度向上剤」としてもよい。また、CDそのものに加えてさらに骨量の増加や骨強度の向上に有用な成分、剤形を保つのに必要な成分等、その他の成分を含む剤であってもよい。
本発明の「ミネラル吸収促進剤」、「骨量増加剤」や「骨強度向上剤」は摂取する動物において効果を示す量を投与すればよい。例えば、摂取する動物がヒトである場合、各剤に含まれ、摂取されるCDの量が0.001～10g/日程度となるように投与されることが好ましい。 The "bone mass increasing agent" and "bone strength improving agent" of the present invention are animals ingested by animals such as humans, mice, rats, rabbits, dogs, cats, horses, sheep, monkeys, and cows. An agent that can increase the weight of bones and improve the strength of bones.
These "bone mass increasing agent" and "bone strength improving agent" may be any agent containing the "mineral absorption promoting agent" of the present invention as an active ingredient, and the "mineral absorption promoting agent" is the CD itself. May use the CD itself as a "bone mass increasing agent" or a "bone strength improving agent". Further, in addition to the CD itself, it may be an agent containing other components such as a component useful for increasing bone mass and bone strength, and a component necessary for maintaining a dosage form.
The "mineral absorption promoter", "bone mass increasing agent" and "bone strength improving agent" of the present invention may be administered in an amount that is effective in the ingesting animal. For example, when the animal to be ingested is a human, it is preferable to administer the CD so that the amount of CD contained in each agent is about 0.001 to 10 g / day.
以下に実施例によって本発明をさらに詳細に説明するが、本発明は、これらの実施例、試験例等に限定されるものではない。
The present invention will be described in more detail below with reference to Examples, but the present invention is not limited to these Examples, Test Examples, and the like.
本発明の実施例、試験例等で使用する試料を次に示した。
＜試料＞
１）α-CD（CAVAMAX W6 Food、株式会社シクロケムバイオ）
２）LS（オリゴのおかげ LS-90P、塩水港精糖株式会社） The samples used in the examples and test examples of the present invention are shown below.
<Sample>
1) α-CD (CAVAMAX W6 Food, Cyclochem Bio Co., Ltd.)
2) LS (Thanks to Oligo LS-90P, Shiomizu Port Refinery Co., Ltd.)
＜試料＞
１）α-CD（CAVAMAX W6 Food、株式会社シクロケムバイオ）
２）LS（オリゴのおかげ LS-90P、塩水港精糖株式会社） The samples used in the examples and test examples of the present invention are shown below.
<Sample>
1) α-CD (CAVAMAX W6 Food, Cyclochem Bio Co., Ltd.)
2) LS (Thanks to Oligo LS-90P, Shiomizu Port Refinery Co., Ltd.)
〔実施例１〕
ミネラル吸収促進剤の製造方法
α-CDをそのままミネラル吸収促進剤として用いた。 [Example 1]
Method for Producing Mineral Absorption Promoter α-CD was used as it was as a mineral absorption promoter.
ミネラル吸収促進剤の製造方法
α-CDをそのままミネラル吸収促進剤として用いた。 [Example 1]
Method for Producing Mineral Absorption Promoter α-CD was used as it was as a mineral absorption promoter.
〔試験例〕
ミネラル吸収促進効果の検討
１．試験方法
3週齢のSDラット（日本SLC社）15匹を1週間の施設順化後、NF群（No Fiber食）、α-CD群（5.5%α-CD含有NF食）、LS群（5.5%LS含有NF食）の3群に分け、各群5匹ずつ、1匹/１ケージで飼育した。本試験は、神戸女子大学の動物実験規程に則って実験が行われた。飼育環境は23±3℃、湿度60±10%、12時間毎に明暗期を設け、餌と水は自由摂取可能とし、実験飼料で8週間飼育した。
各群における実験飼料の配合割合を表１に示した。α-CD又はLS含有量が乾燥飼料中5.5%となるように調製した。各粉末をよく撹拌した後に水100mlを加えてまとめたものを実験飼料とした。
飼育開始から8週間後、各群のラットを一晩絶食させた後イソフルラン麻酔下で解剖し、大腿骨及び盲腸を摘出した。 [Test example]
Examination of mineral absorption promoting effect 1. Test method After acclimatizing 15 3-week-old SD rats (Japan SLC) to the facility for 1 week, the NF group (No Fiber diet), α-CD group (5.5% α-CD-containing NF diet), and LS group (LS group) The animals were divided into 3 groups (NF diet containing 5.5% LS), and 5 animals in each group were bred in 1 cage. This test was conducted in accordance with the Animal Experiment Regulations of Kobe Women's University. The breeding environment was 23 ± 3 ° C, humidity 60 ± 10%, a light-dark period was set every 12 hours, food and water were freely ingested, and the animals were bred with experimental feed for 8 weeks.
Table 1 shows the mixing ratio of the experimental feed in each group. The α-CD or LS content was adjusted to 5.5% in the dry feed. After stirring each powder well, 100 ml of water was added and the mixture was used as an experimental feed.
Eight weeks after the start of breeding, rats in each group were fasted overnight and then dissected under isoflurane anesthesia, and the femur and cecum were removed.
ミネラル吸収促進効果の検討
１．試験方法
3週齢のSDラット（日本SLC社）15匹を1週間の施設順化後、NF群（No Fiber食）、α-CD群（5.5%α-CD含有NF食）、LS群（5.5%LS含有NF食）の3群に分け、各群5匹ずつ、1匹/１ケージで飼育した。本試験は、神戸女子大学の動物実験規程に則って実験が行われた。飼育環境は23±3℃、湿度60±10%、12時間毎に明暗期を設け、餌と水は自由摂取可能とし、実験飼料で8週間飼育した。
各群における実験飼料の配合割合を表１に示した。α-CD又はLS含有量が乾燥飼料中5.5%となるように調製した。各粉末をよく撹拌した後に水100mlを加えてまとめたものを実験飼料とした。
飼育開始から8週間後、各群のラットを一晩絶食させた後イソフルラン麻酔下で解剖し、大腿骨及び盲腸を摘出した。 [Test example]
Examination of mineral absorption promoting effect 1. Test method After acclimatizing 15 3-week-old SD rats (Japan SLC) to the facility for 1 week, the NF group (No Fiber diet), α-CD group (5.5% α-CD-containing NF diet), and LS group (LS group) The animals were divided into 3 groups (NF diet containing 5.5% LS), and 5 animals in each group were bred in 1 cage. This test was conducted in accordance with the Animal Experiment Regulations of Kobe Women's University. The breeding environment was 23 ± 3 ° C, humidity 60 ± 10%, a light-dark period was set every 12 hours, food and water were freely ingested, and the animals were bred with experimental feed for 8 weeks.
Table 1 shows the mixing ratio of the experimental feed in each group. The α-CD or LS content was adjusted to 5.5% in the dry feed. After stirring each powder well, 100 ml of water was added and the mixture was used as an experimental feed.
Eight weeks after the start of breeding, rats in each group were fasted overnight and then dissected under isoflurane anesthesia, and the femur and cecum were removed.
２．盲腸内細菌叢及び短鎖脂肪酸量の解析
上記１にて摘出した盲腸に切り込みを入れて、内容物を搾り出し、盲腸内容物の重量を測定した。盲腸内容物重量を除いたいずれの組織重量も体重のばらつきを考慮し、体重で補正した値を組織重量とした。その後直ちに液体窒素で凍結し-80℃で保存した。
細菌叢分析の段階で解凍した盲腸内容物を混錬して均一化し、委託（株式会社テクノスルガ・ラボ）によりT-RFLP法を用いた細菌叢の解析、SCFAs量の測定及びpHの分析を行った。なお、総SCFAs量は乳酸、コハク酸、酢酸、プロピオン酸及び酪酸の量を合計して算出した。 2. Analysis of the bacterial flora in the cecum and the amount of short-chain fatty acids A cut was made in the cecum excised in 1 above, the contents were squeezed out, and the weight of the contents of the cecum was measured. All tissue weights excluding the weight of the contents of the cecum were taken into consideration for the variation in body weight, and the value corrected by body weight was taken as the tissue weight. Immediately thereafter, it was frozen in liquid nitrogen and stored at -80 ° C.
The contents of the cecum thawed at the stage of bacterial flora analysis are kneaded and homogenized, and the consignment (Technosuruga Lab Co., Ltd.) analyzes the bacterial flora using the T-RFLP method, measures the amount of SCFAs, and analyzes the pH. went. The total amount of SCFAs was calculated by totaling the amounts of lactic acid, succinic acid, acetic acid, propionic acid and butyric acid.
上記１にて摘出した盲腸に切り込みを入れて、内容物を搾り出し、盲腸内容物の重量を測定した。盲腸内容物重量を除いたいずれの組織重量も体重のばらつきを考慮し、体重で補正した値を組織重量とした。その後直ちに液体窒素で凍結し-80℃で保存した。
細菌叢分析の段階で解凍した盲腸内容物を混錬して均一化し、委託（株式会社テクノスルガ・ラボ）によりT-RFLP法を用いた細菌叢の解析、SCFAs量の測定及びpHの分析を行った。なお、総SCFAs量は乳酸、コハク酸、酢酸、プロピオン酸及び酪酸の量を合計して算出した。 2. Analysis of the bacterial flora in the cecum and the amount of short-chain fatty acids A cut was made in the cecum excised in 1 above, the contents were squeezed out, and the weight of the contents of the cecum was measured. All tissue weights excluding the weight of the contents of the cecum were taken into consideration for the variation in body weight, and the value corrected by body weight was taken as the tissue weight. Immediately thereafter, it was frozen in liquid nitrogen and stored at -80 ° C.
The contents of the cecum thawed at the stage of bacterial flora analysis are kneaded and homogenized, and the consignment (Technosuruga Lab Co., Ltd.) analyzes the bacterial flora using the T-RFLP method, measures the amount of SCFAs, and analyzes the pH. went. The total amount of SCFAs was calculated by totaling the amounts of lactic acid, succinic acid, acetic acid, propionic acid and butyric acid.
その結果、T-RFLP法による盲腸内細菌叢の解析ではα-CD群はNF群又はLS群と比べてLactobacillales目の割合が増加した。SCFAs量の分析ではα-CD群はNF群に比べて有意に乳酸、コハク酸、酢酸、プロピオン酸、n-酪酸量及び総SCFAs量が増加することが示され、LS群よりも乳酸、コハク酸、酢酸、プロピオン酸、n-酪酸量及び総SCFAs量の増加が顕著であることが確認できた。α-CD群はNF群に比べて有意に盲腸内pHが低下することが示され、LS群よりも盲腸内pHの低下が顕著であることが確認できた。これらの結果より、α-CDを摂取させた場合、通常食下においてLSよりもSCFAs量が増加する可能性が示唆された。
As a result, in the analysis of the cecal bacterial flora by the T-RFLP method, the proportion of Lactobacillales in the α-CD group was higher than that in the NF group or LS group. Analysis of SCFAs levels showed that the α-CD group significantly increased lactic acid, succinic acid, acetic acid, propionic acid, n-butyric acid and total SCFAs levels compared to the NF group, and lactic acid and succinic acid compared to the LS group. It was confirmed that the amounts of acid, acetic acid, propionic acid, n-butyric acid and total SCFAs increased remarkably. It was shown that the pH in the cecum was significantly lower in the α-CD group than in the NF group, and it was confirmed that the pH in the cecum was significantly lower than that in the LS group. These results suggest that when α-CD is ingested, the amount of SCFAs may increase compared to LS under normal diet.
３．ミネラル吸収の解析
１）実験飼料の摂取量及び糞便量の測定
試験開始44日後に飼育ケージの底にスノコを設置し、45日後から3日間連続で各実験飼料の摂餌量を測定した。また、スノコの下に落ちた糞便を毎日回収し、回収された糞便（3日分）を減圧乾燥して、乾燥後の糞便重量（糞便乾燥重量）を測定した。 3. 3. Analysis of mineral absorption 1) Measurement of experimental feed intake and feces volume A snail was placed at the bottom of the breeding cage 44 days after the start of the test, and the feed intake of each experimental feed was measured 45 days later for 3 consecutive days. In addition, the feces that fell under the drainboard were collected every day, and the collected feces (for 3 days) were dried under reduced pressure, and the weight of the dried feces (dry weight of feces) was measured.
１）実験飼料の摂取量及び糞便量の測定
試験開始44日後に飼育ケージの底にスノコを設置し、45日後から3日間連続で各実験飼料の摂餌量を測定した。また、スノコの下に落ちた糞便を毎日回収し、回収された糞便（3日分）を減圧乾燥して、乾燥後の糞便重量（糞便乾燥重量）を測定した。 3. 3. Analysis of mineral absorption 1) Measurement of experimental feed intake and feces volume A snail was placed at the bottom of the breeding cage 44 days after the start of the test, and the feed intake of each experimental feed was measured 45 days later for 3 consecutive days. In addition, the feces that fell under the drainboard were collected every day, and the collected feces (for 3 days) were dried under reduced pressure, and the weight of the dried feces (dry weight of feces) was measured.
２）ミネラル吸収率の算出
上記１）で測定した各実験飼料の摂餌量と糞便量から、摂取されたカルシウム量（カルシウム摂取量）と吸収されずに排泄されたカルシウム量（カルシウム排泄量）を算出した。
この算出にあたり、まず湿式灰化法によって糞便及び実験飼料中に含まれるミネラル分を抽出した。即ち、ビーカーに乾燥糞便又は実験飼料を秤量し、ホットプレート上に並べ、180℃前後で加熱しながら硝酸、過塩素酸、過酸化水素水を順に添加し、サンプル中の有機成分を除去した。またこの際、糞便又は実験飼料を含まない酸のみを含むブランクも調製した。抽出されたミネラル分を0.01M塩酸で可溶化し、排泄カルシウム測定サンプル及び摂取カルシウム測定サンプルとした。
次に、各サンプル中のカルシウム濃度をメタロアッセイカルシウム測定（OCPC）（メタロジェニクス株式会社）により測定し、次の数式１及び数式２によりカルシウム排泄量及びカルシウム摂取量を算出した。これらの値からブランクの値を引いたものを真のカルシウム排泄量又はカルシウム摂取量とした。 2) Calculation of mineral absorption rate From the amount of food intake and feces of each experimental feed measured in 1) above, the amount of calcium ingested (calcium intake) and the amount of calcium excreted without being absorbed (calcium excretion) Was calculated.
In this calculation, first, minerals contained in feces and experimental feed were extracted by a wet ashing method. That is, dry feces or experimental feed was weighed in a beaker, arranged on a hot plate, and nitric acid, perchloric acid, and hydrogen peroxide solution were added in this order while heating at around 180 ° C. to remove organic components in the sample. At this time, a blank containing only acid without stool or experimental feed was also prepared. The extracted mineral content was solubilized with 0.01 M hydrochloric acid to prepare an excretory calcium measurement sample and an ingestion calcium measurement sample.
Next, the calcium concentration in each sample was measured by metalloassay calcium measurement (OCPC) (Metalogenix Co., Ltd.), and calcium excretion and calcium intake were calculated by the followingformulas 1 and 2. The value obtained by subtracting the blank value from these values was taken as the true calcium excretion amount or calcium intake amount.
上記１）で測定した各実験飼料の摂餌量と糞便量から、摂取されたカルシウム量（カルシウム摂取量）と吸収されずに排泄されたカルシウム量（カルシウム排泄量）を算出した。
この算出にあたり、まず湿式灰化法によって糞便及び実験飼料中に含まれるミネラル分を抽出した。即ち、ビーカーに乾燥糞便又は実験飼料を秤量し、ホットプレート上に並べ、180℃前後で加熱しながら硝酸、過塩素酸、過酸化水素水を順に添加し、サンプル中の有機成分を除去した。またこの際、糞便又は実験飼料を含まない酸のみを含むブランクも調製した。抽出されたミネラル分を0.01M塩酸で可溶化し、排泄カルシウム測定サンプル及び摂取カルシウム測定サンプルとした。
次に、各サンプル中のカルシウム濃度をメタロアッセイカルシウム測定（OCPC）（メタロジェニクス株式会社）により測定し、次の数式１及び数式２によりカルシウム排泄量及びカルシウム摂取量を算出した。これらの値からブランクの値を引いたものを真のカルシウム排泄量又はカルシウム摂取量とした。 2) Calculation of mineral absorption rate From the amount of food intake and feces of each experimental feed measured in 1) above, the amount of calcium ingested (calcium intake) and the amount of calcium excreted without being absorbed (calcium excretion) Was calculated.
In this calculation, first, minerals contained in feces and experimental feed were extracted by a wet ashing method. That is, dry feces or experimental feed was weighed in a beaker, arranged on a hot plate, and nitric acid, perchloric acid, and hydrogen peroxide solution were added in this order while heating at around 180 ° C. to remove organic components in the sample. At this time, a blank containing only acid without stool or experimental feed was also prepared. The extracted mineral content was solubilized with 0.01 M hydrochloric acid to prepare an excretory calcium measurement sample and an ingestion calcium measurement sample.
Next, the calcium concentration in each sample was measured by metalloassay calcium measurement (OCPC) (Metalogenix Co., Ltd.), and calcium excretion and calcium intake were calculated by the following
これらの真の各カルシウム量から次の数式３及び数式４によりカルシウム吸収率を算出し、結果を図１に示した。その結果、図１に示されるようにα-CDを含有する実験飼料を摂取した群（α-CD群）はα-CDやLSを含有しない実験飼料を摂取した群（NF群）に比べて有意にカルシウムの吸収率が向上することが示された（p<0.05）。また、α-CDを含有する実験飼料を摂取した群（α-CD群）は、LSを含有する実験飼料を摂取した群（LS群）よりもカルシウムの吸収率が向上することも確認できた。
The calcium absorption rate was calculated from each of these true amounts of calcium by the following formulas 3 and 4, and the results are shown in FIG. As a result, as shown in FIG. 1, the group that ingested the experimental diet containing α-CD (α-CD group) was compared with the group that ingested the experimental diet not containing α-CD or LS (NF group). It was shown that the absorption rate of calcium was significantly improved (p <0.05). It was also confirmed that the group that ingested the experimental diet containing α-CD (α-CD group) had a higher calcium absorption rate than the group that ingested the experimental diet containing LS (LS group). ..
４．骨量及び骨強度の検討
１）骨量
上記１にて摘出した大腿骨から付着している筋組織を切除し、重量を測定した。その後、個体ごとの体重のばらつきを考慮し、体重で補正した値を大腿骨重量とした。各実験飼料を摂取した群における大腿骨重量（平均）を比較したところ、図２に示されるように、α-CD群はNF群に比べて有意に骨量が増加することが示され、LS群よりも骨量の増加が顕著であることが確認できた（p<0.01）。 4. Examination of bone mass and bone strength 1) Bone mass The muscle tissue attached to the femur excised in 1 above was excised and the weight was measured. Then, in consideration of the variation in body weight of each individual, the value corrected by the body weight was taken as the femur weight. Comparing the femur weights (average) in the groups that received each experimental feed, it was shown that the α-CD group significantly increased bone mass compared to the NF group, as shown in FIG. 2, and LS It was confirmed that the increase in bone mass was more remarkable than in the group (p <0.01).
１）骨量
上記１にて摘出した大腿骨から付着している筋組織を切除し、重量を測定した。その後、個体ごとの体重のばらつきを考慮し、体重で補正した値を大腿骨重量とした。各実験飼料を摂取した群における大腿骨重量（平均）を比較したところ、図２に示されるように、α-CD群はNF群に比べて有意に骨量が増加することが示され、LS群よりも骨量の増加が顕著であることが確認できた（p<0.01）。 4. Examination of bone mass and bone strength 1) Bone mass The muscle tissue attached to the femur excised in 1 above was excised and the weight was measured. Then, in consideration of the variation in body weight of each individual, the value corrected by the body weight was taken as the femur weight. Comparing the femur weights (average) in the groups that received each experimental feed, it was shown that the α-CD group significantly increased bone mass compared to the NF group, as shown in FIG. 2, and LS It was confirmed that the increase in bone mass was more remarkable than in the group (p <0.01).
２）骨強度
上記４、１）にて骨量を測定した大腿骨の中央部を骨強度/皮膚破断強度試験機TK-252D（室町機械株式会社）により、速度3mm/min、支点間距離1cmの条件で破断し、測定された最大荷重より骨強度を調べた。
その結果、図３に示されるようにα-CD群はNF群に比べて有意に骨強度が向上することが示され、LS群よりも骨強度の向上が顕著であることが確認できた（p<0.05）。 2) Bone strength The central part of the femoral bone whose bone mass was measured in 4 and 1) above was measured by the bone strength / skin breaking strength tester TK-252D (Muromachi Kikai Co., Ltd.) at a speed of 3 mm / min and a distance between fulcrums of 1 cm. The bone strength was examined from the measured maximum load after fracture under the conditions of.
As a result, as shown in FIG. 3, it was shown that the α-CD group significantly improved the bone strength as compared with the NF group, and it was confirmed that the improvement in the bone strength was remarkable as compared with the LS group (). p <0.05).
上記４、１）にて骨量を測定した大腿骨の中央部を骨強度/皮膚破断強度試験機TK-252D（室町機械株式会社）により、速度3mm/min、支点間距離1cmの条件で破断し、測定された最大荷重より骨強度を調べた。
その結果、図３に示されるようにα-CD群はNF群に比べて有意に骨強度が向上することが示され、LS群よりも骨強度の向上が顕著であることが確認できた（p<0.05）。 2) Bone strength The central part of the femoral bone whose bone mass was measured in 4 and 1) above was measured by the bone strength / skin breaking strength tester TK-252D (Muromachi Kikai Co., Ltd.) at a speed of 3 mm / min and a distance between fulcrums of 1 cm. The bone strength was examined from the measured maximum load after fracture under the conditions of.
As a result, as shown in FIG. 3, it was shown that the α-CD group significantly improved the bone strength as compared with the NF group, and it was confirmed that the improvement in the bone strength was remarkable as compared with the LS group (). p <0.05).
５．まとめ
上記１～４の結果から示されるように、CDそのものがLSと同等又はそれ以上のカルシウム等のミネラル吸収を促進する効果を有することが確認できた。さらに、CDそのものが骨量の増加や骨強度の向上にも顕著な効果を有することが示された。 5. Summary As shown from the results of 1 to 4 above, it was confirmed that CD itself has the effect of promoting the absorption of minerals such as calcium equal to or higher than that of LS. Furthermore, it was shown that CD itself has a remarkable effect on increasing bone mass and bone strength.
上記１～４の結果から示されるように、CDそのものがLSと同等又はそれ以上のカルシウム等のミネラル吸収を促進する効果を有することが確認できた。さらに、CDそのものが骨量の増加や骨強度の向上にも顕著な効果を有することが示された。 5. Summary As shown from the results of 1 to 4 above, it was confirmed that CD itself has the effect of promoting the absorption of minerals such as calcium equal to or higher than that of LS. Furthermore, it was shown that CD itself has a remarkable effect on increasing bone mass and bone strength.
本発明によりLSと同等又はそれ以上のミネラル吸収を促進する効果を有するものの提供が可能となった。本発明のネラル吸収促進剤はそのまま食品、健康食品、医薬部外品や医薬品等として利用したり、骨量増加剤や骨強度向上剤等の有効成分として利用したりすることができ、様々な用途に使用できる。
According to the present invention, it has become possible to provide a substance having an effect of promoting mineral absorption equal to or higher than that of LS. The neral absorption promoter of the present invention can be used as it is as a food, a health food, a quasi-drug, a pharmaceutical product, etc., or can be used as an active ingredient such as a bone mass increasing agent or a bone strength improving agent. Can be used for various purposes.
Claims (4)
- シクロデキストリンを有効成分として含むミネラル吸収促進剤。 A mineral absorption promoter containing cyclodextrin as an active ingredient.
- ミネラルがカルシウムである請求項１に記載のミネラル吸収促進剤。 The mineral absorption promoter according to claim 1, wherein the mineral is calcium.
- 請求項１又は２に記載のミネラル吸収促進剤を有効成分として含む骨量増加剤。 A bone mass-increasing agent containing the mineral absorption-promoting agent according to claim 1 or 2 as an active ingredient.
- 請求項１又は２に記載のミネラル吸収促進剤を有効成分として含む骨強度向上剤。
A bone strength improving agent containing the mineral absorption promoter according to claim 1 or 2 as an active ingredient.
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| WO2018016100A1 (en) * | 2016-07-22 | 2018-01-25 | 一般社団法人 Ｕｎｉｃａｌ | Production method for granules of calcium salt, and said granules |
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2021
- 2021-03-01 WO PCT/JP2021/007771 patent/WO2021177247A1/en active Application Filing
- 2021-03-01 JP JP2022504361A patent/JPWO2021177247A1/ja active Pending
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